SIRT1 Regulation in Ageing and Obesity

• Published in: Mechanisms of ageing and development Vol. 188; p. 111249
• Main Authors: Pardo, Patricia S., Boriek, Aladin M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.06.2020
• Subjects: Ageing; Obesity; SIRT1; Obesity; SIRT1; Ageing
• ISSN: 0047-6374; 1872-6216; 1872-6216
• DOI: 10.1016/j.mad.2020.111249

•Reduced SIRT1 expression or activity in age and obesity associated diseases.•Regulation of Sirt1 transcription and SIRT1 RNA and protein stability as determinants of lower SIRT1 expression in ageing and obesity.•A decline in NAD levels contributes to low SIRT1 activity in ageing.•Modulation of SIRT1 activity and NAD availability as therapeutic strategies to prevent and ameliorate age and obesity associated disorders. Ageing and obesity have common hallmarks: altered glucose and lipid metabolism, chronic inflammation and oxidative stress are some examples. The downstream effects of SIRT1 activity have been thoroughly explored, and their research is still in expanse. SIRT1 activation has been shown to regulate pathways with beneficiary effects on 1) ageing and obesity-associated metabolic disorders such as metabolic syndrome, insulin resistance and type-II diabetes with, 2) chronic inflammatory processes such as arthritis, atherosclerosis and emphysema, 3) DNA damage and oxidative stress with impact on neurodegenerative diseases, cardiovascular health and some cancers. This knowledge intensified the interest in uncovering the mechanisms regulating the expression and activity of SIRT1. This review focuses on the upstream regulatory mechanisms controlling SIRT1, and how this knowledge could potentially contribute to the development of therapeutic interventions.